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Cellular messenger RNA (mRNA) of higher eukaryotes and many viral RNAs are methylated at the N-7 and 2'-O positions of the 5' guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability, the function of 2'-O methylation has remained uncertain since its discovery 35 years ago. Here we show that a West Nile virus (WNV) mutant (E218A) that lacks 2'-O MTase activity was attenuated in wild-type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signalling. 2'-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISGs) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2'-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and, specifically, IFIT proteins. Our results demonstrate that the 2'-O methylation of the 5' cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2'-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA probably serves as an example for pattern recognition and restriction of propagation of foreign viral RNA in host cells.

The synapse between the giant interneurone and the motor giant axon of the crayfish is a well-known example of the rare class of current-rectifying electrotonic synapses. One early proposal for the basis of this rectification was that rectifying junctions are like diodes. Biological correlates of diodes can exist, such as constant-field channels which rectify by very high-speed rearrangements of charge carriers, but these require high selectivity and large concentration gradients. Electrotonic synapses are believed to be composed of wide-bore (1-2 nm) gap-junction channels which have poor selectivity and bridge similar intracellular compartments. An alternative mechanism for rectification would be by voltage-dependent gates that sense trans-synaptic potential. These two mechanisms can be distinguished because a diode should rectify instantaneously (on a biological time-scale) while a gated channel should show kinetic processes. Although a gating model is more consistent with the known behaviour of channels than a diode model, previous work has failed to find any time course for the rectification. We have now developed a high-quality voltage clamp and by working at reduced temperatures we are able to demonstrate channel kinetics. These results support the hypothesis that this rectifying synapse contains voltage-dependent gates.

THE effect of gravitational radiation on an elastic body has been previously investigated1. The component varying with time of the Riemann tensor (R iojo) associated with the gravitational field acts as a driving term in the wave equation for the strain or displacement. It was proposed1 that the normal modes of the Earth or a laboratory mass be used as a detector of gravitational radiation. Experiments to measure the interstellar gravitational radiation at kilocycle frequencies are at present in progress at the University of Maryland.